Distinct Wnt signaling pathways have opposing roles in appendage regeneration

Cristi L. Stoick-Cooper; Gilbert Weidinger; Kimberly J. Riehle; Charlotte Hubbert; Michael B. Major; Nelson Fausto; Randall T. Moon

doi:10.1242/dev.001123

journal article Feb 01, 2007

Distinct Wnt signaling pathways have opposing roles in appendage regeneration

Cristi L. Stoick-Cooper Gilbert Weidinger Kimberly J. Riehle Charlotte Hubbert Michael B. Major

Nelson Fausto Randall T. Moon

Development Vol. 134 No. 3 pp. 479-489 · The Company of Biologists

View at Publisher Save 10.1242/dev.001123

Abstract

In contrast to mammals, lower vertebrates have a remarkable capacity to regenerate complex structures damaged by injury or disease. This process,termed epimorphic regeneration, involves progenitor cells created through the reprogramming of differentiated cells or through the activation of resident stem cells. Wnt/β-catenin signaling regulates progenitor cell fate and proliferation during embryonic development and stem cell function in adults,but its functional involvement in epimorphic regeneration has not been addressed. Using transgenic fish lines, we show that Wnt/β-catenin signaling is activated in the regenerating zebrafish tail fin and is required for formation and subsequent proliferation of the progenitor cells of the blastema. Wnt/β-catenin signaling appears to act upstream of FGF signaling, which has recently been found to be essential for fin regeneration. Intriguingly, increased Wnt/β-catenin signaling is sufficient to augment regeneration, as tail fins regenerate faster in fish heterozygous for a loss-of-function mutation in axin1, a negative regulator of the pathway. Likewise, activation of Wnt/β-catenin signaling by overexpression of wnt8 increases proliferation of progenitor cells in the regenerating fin. By contrast, overexpression of wnt5b(pipetail) reduces expression of Wnt/β-catenin target genes,impairs proliferation of progenitors and inhibits fin regeneration. Importantly, fin regeneration is accelerated in wnt5b mutant fish. These data suggest that Wnt/β-catenin signaling promotes regeneration,whereas a distinct pathway activated by wnt5b acts in a negative-feedback loop to limit regeneration.

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Details

Published: Feb 01, 2007
Vol/Issue: 134(3)
Pages: 479-489

Authors

C

Cristi L. Stoick-Cooper

Howard Hughes Medical Institute, Department of Pharmacology, Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA.; Graduate Program in Neurobiology and Behavior, University of Washington School of Medicine, Seattle, WA 98195, USA.

G

Gilbert Weidinger

Howard Hughes Medical Institute, Department of Pharmacology, Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA.

K

Kimberly J. Riehle

Department of Surgery, University of Washington School of Medicine, Seattle,WA 98195, USA.; Department of Pathology, University of Washington School of Medicine, Seattle,WA 98195, USA.

C

Charlotte Hubbert

Howard Hughes Medical Institute, Department of Pharmacology, Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA.

M

Michael B. Major

Howard Hughes Medical Institute, Department of Pharmacology, Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA.

N

Nelson Fausto

Department of Pathology, University of Washington School of Medicine, Seattle,WA 98195, USA.

R

Randall T. Moon

Howard Hughes Medical Institute, Department of Pharmacology, Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA.

Cite This Article

Cristi L. Stoick-Cooper, Gilbert Weidinger, Kimberly J. Riehle, et al. (2007). Distinct Wnt signaling pathways have opposing roles in appendage regeneration. Development, 134(3), 479-489. https://doi.org/10.1242/dev.001123

Distinct Wnt signaling pathways have opposing roles in appendage regeneration

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